The objective of this research proposal is to evaluate the effects of phenylalanine ammonia-lyase (PAL) and phenylalanine restiction on leukemias and melanomas in mice. As a source of enzyme, the induction of PAL in the yeast Rhodotorula glutinis has been investigated. PAL has been highly purified by salt fractionation and column chromatography and analyzed for purity, isoelectric point, and amino acid composition. PAL markedly inhibied leukemic cell growth in vitro and gave 40% cures against a murine leukemia in vivo. Plasma levels of PAL, phenylalanine, and tyrosine have been determined as a function of time following single and multiple injections of the enzyme. Further evaluations of the therapeutic effect of PAL against spontaneous leukemias and melanomas are currently under investigation.